My primary goal is to develop a vigorous research program to study cellular and molecular mechanisms involved in the initiation and/or progression vascular disorders upon exposure to environmental/occupational toxins. Although during his first two years at Texas A&M University Dr. Ramos was allowed to focus on research activities, his teaching and administrative commitment will increase significantly to 30-40% of his time in the coming years. A RCDA would allow Dr. Ramos to continue to devote most of his efforts to research and research-related activities. Under such conditions, Dr. Ramos should be able to make significant contributions to the field of toxicology, as well as vascular cell biology. Dr. Ramos is an Associate Professor of Toxicology in the Department of Physiology and Pharmacology, College of Veterinary Medicine at Texas A&M University. He also holds joint appointments in the Department of Medical Physiology, College of Medicine and the Texas Agricultural Experiment Station. Approximately 750 square feet of well-equipped laboratory space with an adjacent office are available to the principal investigator. Additional laboratory and office space are available within the Department of Medical Physiology. The Faculty of Toxicology at Texas A&M University consists of 13 toxicologists within the College of Veterinary Medicine, as well as 27 members from other Colleges within the University System. This group encompasses scientists with a diverse background which share a primary interest in Toxicology. The Department of Medical Physiology consists of 8 faculty members sharing broad interests in the area of vascular cell biology. The natural overlap of these two groups with the research interests of the principal investigator provide a rich scientific environment for the professional development of the applicant. In this application, experiments are proposed to test the hypothesis that allylamine and benzo(a)pyrene induce erratic expression of oncogenes to cause the phenotypic modulation of smooth muscle cells from a contractile to a more synthetic state. Phenotypic expression is defined by morphologic, ultrastructural, biochemical and functional criteria. The status of the phosphoinositide signal transduction system will be evaluated to determine if alterations in turnover are involved in the expression of the synthetic phenotype. Studies will be conducted to determine if erratic expression of cellular oncogenes in vivo and in vitro is associated with chemical treatment. The data generated from these studies can be used to better understand the role that exposure to ubiquitous environmental contaminants plays in the development of atherosclerosis and other pathological changes of the vascular wall.